A great number of studies have been made on the drug delivery system that enables effective medicinal treatment by delivering a drug administered to the living body to desired tissues in desired amounts at desired times. Many drug carriers have been reported by now, and out of them particulate carriers such as liposome and lipid microsphere are among those drug carriers that strongly attract general attention. Generally speaking, when particulate carriers like liposome are administered into a blood-vessel, it is readily captured, as is well known, by the reticuloendothelial system represented by liver and spleen. This phenomenon forms a big problem when such preparations are utilized as a release-controlling carrier that allows release of the drug in a controlled manner or as a targeting carrier that allows delivery of the drug to desired organs, e.g., in intravenous administration.
Such drug carriers as described above that, in systemical administration such as intravenous administration, are resistant to capture by the reticuloendothelial system, and show improved microcirculation activity within the living body have been studied so far. Taking as an example liposomes in respect of which their membrane components may be altered in their combination, to improve microcirculation activity, cholesterol is added (Biochem. Pharmacol., 32, 609(1983)), or a lipid having a high phase-transition temperature is used (Biochem. Biophys. Acta, 839, 1(1985)). Also there is a case where, as the size of liposomes can be relatively easily controlled, liposomes are reduced in size to improve microcirculation (J. Pharmacol. Exp. Therap., 226. 539(1983)).
In addition, recently there are communications reporting that ganglioside or a glycolipid derived from the cell membrane, or glycophorin or a glycoprotein from the red blood cell membrane is incorporated into the liposome membrane for their reorganization in order to improve microcirculation. As an example for the former, there is an article reporting that the use of ganglioside GM.sub.1 gives liposomes an increased resistance to capture by the reticuloendothelial system, to ensure relatively stable microcirculation of the liposome in blood (Biochim. Biophys. Acta, 981, 27(1989), U.S. Pat. No. 4,837,028 (Jun. 6, 1989)). As an example for the latter, there is an article reporting that the use of glycophorin derived from human red blood cells brings about the same effect (Proceedings of the 9th Symposium of "Biomembrane and Drug Interaction", p. 193, Tokyo, 1986). There are other similar reports describing the reorganization into a liposome membrane of a glycolipid derived from fetuin or a blood serum protein (Chem. Pharm. Bull., 36, 4187(1988)), and the use as liposome membrane components of sialic acid bound to a polysaccharide such as pullulan or amylopectin together with cholesterol residue (Chem. Lett., pp. 1781(1988)).
As described above, a large number of studies have indeed been made on the manufacture of liposome preparations that can achieve a microcirculation in the blood circulatory system, by circumventing the capture by the reticuloendothelial system. But, the current state is far from the desired goal in that carriers with a glycolipid or glycoprotein as their component in such a manner as stated above are still inadequate in industrial productivity and practicability, taking into consideration the mass production and material cost aspect.
The present invention aims at providing novel substances that are resistant to capture by the reticuloendothelial system such as liver, spleen, etc., capable of conferring microcirculation activity in vivo to particulate carriers such as liposome, and further allow mass production of industrially reproducible quantity.